Osteosarcoma is the most common primary malignant bone tumor with a five-year survival of approximately fifteen percent following treatment by surgery and/or radiation therapy. Newer therapeutic approaches to this and other primary and metastatic bone tumors involve chemotherapy, immunotherapy, and bone allograft reconstruction of skeletal defects following less radical ablative surgery. Because of limitations imposed upon the size of the patient populations involved with each form of treatment by a large number of treatment protocols, and because of the ethical constraints of human experimentation, animal models have been developed by the principal investigator to study the immunobiology of osteosarcoma and bone allografts. The objectives of this project are to evaluate currently proposed therapeutic protocols involving surgery, irradiation, chemotherapy, and immunotherapy in an animal model bearing clinical, histological, and immunobiological similarities to the human disease. The model is an initially localized virally induced (MSV) lesion produced in inbred neonatal rats (Wistar-Lewis). Using survival, histological onset of pulmonary metastatis, and an isotope release microcytotoxicity assay for humoral and cellular immunity as parameters of success, data will support the most efficacious treatment protocol, discourage less productive approaches, and perhaps suggest new directions for future therapeutics. A rabbit model has also been established by the principal investigator in which the immunobiology of bone allografts required for post-ablation reconstruction can be evaluated. There is already data to suggest that the immunological response of the host is influenced by the methods of allograft preservation. This response can be measured by an isotope release microcytotoxicity assay and will be correlated with histological, radiological, and biomechanical information in order to clearly define the most acceptable method of bone allograft processing and long-term preservation. Antigenicity of cartilage matrix and the effect of chemotherapy on bone biology and biomechanics are also being studied.